It is the purpose of this project to analyze and develop new and difficult cell systems in culture. We have developed and are attempting to exploit applications of normal rat thyroid cell cultures. These cells are hormone dependent. They synthesize and secrete a very large protein product, thyro-globulin. They concentrate iodide 100-fold from the medium. They offer a unique opportunity to study secretion, ion uptake and cAMP response. These are being studied in our lab and in other labs, however, our approach is primarily to use electrophysiological techniques. We are attempting to study long term regulation of membrane potential and its relationship to secretion and hormone levels. We are also studying neurons and neuroblasts in cell culture. There are too few mammalian cell systems where "blast" cells can be observed in transition to mature, differentiated cells. We have tried this in nerve cells using cellular hybridization and cellular transformation (with ts SV40 viruses) and by using little known cell systems in which blast cells persist throughout life (olfactory epithelium). We are especially interested in the development of electrophysiological competence and in the development of chemical identity (specificity).